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Updated: Jul 20, 2026

Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Deletion/insertion polymorphism of the angiotensin-converting enzyme gene and white matter hyperintensities in
Nitin Purandare1, Richard C Oude Voshaar, Yvonne Davidson
1Division of Psychiatry, Education and Research Center, South Manchester University Hospital, Manchester, United Kingdom. nitin.purandare@manchester.ac.uk
Objectives:
To examine the association between the angiotensin-converting enzyme (ACE) deletion/insertion (D/I) polymorphism and white matter hyperintensities (WMHs) in patients with dementia.
Design:
Observational pilot study with adjustment for potential confounders using analysis of covariance.
Setting:
Secondary care old-age psychiatry services in greater Manchester, United Kingdom.
Participants:
Ninety-seven patients with dementia: 49 with Alzheimer's disease (AD, National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria) and 48 with vascular dementia (VaD, National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences criteria).
Measurements:
The ACE D/I polymorphism, WMHs (deep WMHs (DWMHs) and periventricular hyperintensities (PVHs)) on T2-weighted magnetic resonance imaging, and potential cardiovascular confounders.
Results:
The D/D polymorphism of the ACE genotype was associated with severity of DWMH (P = .005) but not PVH (P = .34), corrected for age, cardiovascular risk factors, and type of dementia. Post hoc analyses were limited by statistical power but suggested an interaction with the apolipoprotein E epsilon4 allele.
Conclusion:
The results support previous observations that genetic factors influence the development of WMHs in dementia. The involvement of the ACE D/I polymorphism in the pathogenesis of DWMHs in dementia (AD and VaD), by a mechanism that is independent of its association with cardiovascular risk factors, should be confirmed in a large population-based sample.
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